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Pharma Respi > Drugs for TB > Flashcards

Drugs for TB Flashcards

1
Q

What is the percentage of individuals infected with M. tuberculosis that will have containment of the disease?

A

More than 90%

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2
Q

Enumerate at least 4 challenges in treating Mycobacteria.

A

Any four of the following: Grow slowly, resistance to drugs, dormancy, lipid-rich cell wall, intracellular pathogens

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3
Q

Why are antibiotics that are most active against rapidly growing cells relatively ineffective against Mycobacteria?

A

Mycobacteria grow slowly

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4
Q

Why is the lipid-rich cell wall of Mycobacteria a challenge in treatment?

A

It is impermeable to many agents.

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5
Q

What is the approximate number of drug-resistant mutants per Mycobacterium tuberculosis bacillus?

A

1 in 10^6

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6
Q

What are the implications of the fact that some second-line drugs for TB are commonly used antibiotics for URTI and UTI?

A

Overuse of these antibiotics could lead to the development of resistance in M. tuberculosis.

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7
Q

Why is the use of multiple drugs in combination more effective than single-drug therapy for TB?

A

The probability of a bacillus being resistant to multiple drugs is much lower than the probability of it being resistant to a single drug.

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8
Q

What is the probability of a Mycobacterium tuberculosis bacillus being resistant to both isoniazid and rifampicin?

A

1 in 10^12

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9
Q

For how long should isoniazid and rifampicin be administered to cure 95-98% of pulmonary TB caused by susceptible strains?

A

9 months

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10
Q

What is the effect of adding pyrazinamide to isoniazid and rifampicin therapy for the first 2 months?

A

It shortens the treatment duration to 6 months.

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11
Q

What is the effect of adding ethambutol to the standard isoniazid and rifampicin regimen?

A

It does not shorten treatment but increases coverage for resistance.

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12
Q

Which TB subpopulation is targeted by streptomycin?

A

TB subpopulations inside cavities

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13
Q

Why is pyrazinamide effective against TB subpopulations in closed lesions and inside macrophages?

A

PZA prefers an acidic milieu, which is found in closed lesions and macrophages.

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14
Q

What is the drug of choice for treating TB?

A

Isoniazid

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15
Q

Isoniazid is structurally similar to what vitamin?

A

Pyridoxine

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16
Q

Against what type of M. tuberculosis bacilli is isoniazid bactericidal?

A

Actively/rapidly growing bacilli

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17
Q

What enzyme activates isoniazid?

A

KatG (mycobacterial catalase-peroxidase)

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18
Q

Mutations in which two genes are associated with isoniazid resistance?

A

InhA and KatG

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19
Q

What enzyme is inhibited by activated isoniazid?

A

Enoyl-acyl carrier protein reductase (InhA)

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20
Q

What advice is given to patients regarding food intake when taking isoniazid?

A

Take isoniazid at least 30 minutes before food.

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21
Q

How is the metabolism of isoniazid genetically determined?

A

By the rate of acetylation by liver N-acetyl transferase. There are fast and slow acetylators.

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22
Q

What is the typical daily dose of isoniazid?

A

5 mg/kg/day

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23
Q

What supplement is recommended for patients taking isoniazid, and why?

A

Pyridoxine (25-50 mg/day), to prevent peripheral neuropathy due to relative pyridoxine deficiency

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24
Q

What is the most severe side effect of isoniazid?

A

Hepatitis

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25
Q

List three groups of individuals who are at increased risk of developing isoniazid-induced hepatitis.

A

Any three of the following: Elderly, alcoholic drinkers, pregnant and postpartum individuals, patients taking rifampicin

26
Q

What are the symptoms of isoniazid-induced hepatitis?

A

Loss of appetite, nausea, vomiting, jaundice, RUQ pain

27
Q

What percentage of patients develop isoniazid-induced hepatitis?

A

0.01

28
Q

What is the cause of isoniazid-induced peripheral neuropathy?

A

Relative pyridoxine (Vitamin B6) deficiency

29
Q

List five conditions that predispose patients to isoniazid-induced peripheral neuropathy.

A

Any five of the following: Slow acetylators, malnutrition, alcoholism, diabetes, AIDS, uremia

30
Q

How is isoniazid-induced peripheral neuropathy reversed?

A

By administration of pyridoxine (10 mg/day)

31
Q

What is the characteristic finding in urine, sweat, and tears of patients taking rifampicin?

A

Orange color

32
Q

What is the mechanism of action of rifampicin?

A

Binds to the β-subunit of bacterial DNA-dependent RNA polymerase and inhibits RNA synthesis.

33
Q

Mutations in which gene are responsible for rifampicin resistance?

A

rpoB

34
Q

What type of cells does rifampicin readily penetrate?

A

Most tissues and phagocytic cells

35
Q

What is the half-life of rifampicin?

A

3.5 hours

36
Q

What is the effect of rifampicin on cytochrome P450 enzymes?

A

Potent inducer

37
Q

What is the recommended daily dose of rifampicin?

A

10 mg/kg/day

38
Q

What type of mycobacterial infections is rifampicin effective against?

A

Atypical mycobacterial infections

39
Q

What effect does rifampicin have on serum levels of other drugs?

A

Lowers serum levels

40
Q

Why is it necessary to adjust the dose of other medications when they are used concurrently with rifampicin?

A

Rifampicin induces cytochrome P450, which increases the metabolism and clearance of other drugs.

41
Q

What is pyrazinamide a relative of?

A

Nicotinamide

42
Q

At what pH is pyrazinamide most active?

A

Acidic pH 5.5

43
Q

What enzyme converts pyrazinamide to its active form?

A

Pyrazinamidase (PncA)

44
Q

What is the active form of pyrazinamide?

A

Pyrazinoic acid

45
Q

What enzyme is inhibited by the active form of pyrazinamide?

A

Fatty acid synthetase I (FAT I)

46
Q

What is the half-life of pyrazinamide?

A

8-11 hours

47
Q

What is the recommended daily dose of pyrazinamide?

A

25 mg/kg/day

48
Q

What is the role of pyrazinamide in shortening the duration of TB therapy?

A

It is a sterilizing agent used during the first 2 months of therapy that targets residual intracellular organisms.

49
Q

What is the most common adverse reaction associated with pyrazinamide?

A

Hepatotoxicity

50
Q

What other adverse reactions are associated with pyrazinamide?

A

Nausea, vomiting, drug fever, hyperuricemia

51
Q

Is hyperuricemia a reason to stop pyrazinamide treatment?

A

No, it is not usually a reason to halt treatment.

52
Q

What is the mechanism of action of ethambutol?

A

Inhibits mycobacterial arabinosyl transferases

53
Q

What operon encodes the arabinosyl transferases inhibited by ethambutol?

A

embCAB operon

54
Q

What is the bactericidal or bacteriostatic nature of ethambutol?

A

Bacteriostatic

55
Q

What is the half-life of ethambutol?

A

4 hours

56
Q

What is the recommended daily dose of ethambutol?

A

15-25 mg/kg/day

57
Q

What is the most common serious adverse reaction associated with ethambutol?

A

Retrobulbar neuritis

58
Q

What visual disturbances are associated with ethambutol-induced retrobulbar neuritis?

A

Loss of visual acuity and red-green color blindness

59
Q

In what population is ethambutol relatively contraindicated?

A

Very young children

60
Q

Streptomycin interferes with the translation of mRNA transcripts in M. tuberculosis by binding to what ribosomal protein?

A

S12

Pharma Respi (1 decks)

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